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Paper of the Month - September 2025
selected by the BMAS Scientific Board

Implication of bone marrow adipose tissue in bone homeostasis during osteoarthritis

Natalia Zapata-Linares1, Indira Toillon1, Kristell Wanherdrick1, Audrey Pigenet1, Fanny Duhalde2, Marie Binvignat1, Patxi San Martin-Uriz3, Loïc Louvet4, Maria E Calleja-Cervantes5, Olfa Ghali Mhenni4, Clément Guibert6, Geoffroy Nourissat1, Alexis Nogier7, Damien Leterme4, Odile Broux4, Paul Magneron1, Felipe Prosper8, Christophe Chauveau4, Jessem Landoulsi6, Francis Berenbaum9, Juan R Rodriguez-Madoz10, Marie-Hélène Lafage-Proust11, Stéphanie Lucas4, Xavier Houard12
  • 1Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, F-75012 Paris, France.
  • 2Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, F-75012 Paris, France; Sorbonne Université, CNRS, Laboratoire de
    Réactivité de Surface, LRS, F-75005, Paris, France.
  • 3Hemato-Oncology Program. CIMA Universidad de Navarra-IdiSNA, Pamplona, Spain.
  • 4Marrow Adiposity and Bone Lab (MABLab) ULR4490, Université du Littoral Côte d’Opale, F-62200 Boulogne sur Mer, Univ. Lille, F-59000 Lille, CHU Lille, F-59000 Lille, France.
  • 5Hemato-Oncology Program. CIMA Universidad de Navarra-IdiSNA, Pamplona, Spain; Computational Biology Program, CIMA Universidad de
    Navarra-IdiSNA, Pamplona, Spain.
  • 6Sorbonne Université, CNRS, Laboratoire de Réactivité de Surface, LRS, F-75005, Paris, France.
  • 7Clinique Maussins-Nollet, F-75019 Paris, France.
  • 8Hemato-Oncology Program. CIMA Universidad de Navarra-IdiSNA, Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain; Hematology and Cell Therapy Department, Clinica Universidad de Navarra, IdiSNA, Pamplona, Spain; Cancer Center
    Universidad de Navarra (CCUN), Pamplona, Spain.
  • 9Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA,F-75012 Paris, France; Rheumatology Department, AP-HP Saint-AntoineHospital, 184, Rue du Faubourg Saint-Antoine, 75012 Paris, France.
  • 10Hemato-Oncology Program. CIMA Universidad de Navarra-IdiSNA, Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain; Cancer Center Universidad de Navarra (CCUN), Pamplona, Spain.
  • 11 Université de Lyon – Université Jean Monnet, INSERM U1059, Faculté de Médecine, F-42270 Saint-Priest en Jarez, France.
  • 12Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA,
    F-75012 Paris, France. Electronic address:

Correspondence: Xavier Houard, xavier.houard@sorbonne-universite.fr.

Osteoarthritis and Cartilage, August 2025; 33(8):951-964

Abstract

Objective: To explore the role of bone marrow adipocytes (BMAds) in osteoarthritis (OA).

Methods: Male and female C57BL/6 mice (n=4/group) underwent meniscectomy (MNX) or SHAM surgery. OA was determined using Osteoarthritis Research Society International (OARSI) score, and the number of perilipin+ adipocytes was quantified. Mesenchymal Stromal Cells (MSCs) from MNX and SHAM mice were differentiated into osteoblasts and adipocytes. Human adipocytes and MSCs (n=8) were enzymatically isolated from epiphyseal and metaphyseal marrow, and from subcutaneous adipose tissue (SCAT) of hip OA patients. Human OA MSCs were differentiated into osteoblasts and adipocytes (OA-Diff-hAdipo). Gene expression patterns of epiphyseal and metaphyseal BMAds, SCAT adipocytes and OA-Diff-hAdipo were evaluated by RNAseq (n=4). The effect conditioned media from OA epiphyseal bone (n=5) on the alkaline phosphatase (ALP) activity and mineralization kinetics was assessed in vitro.

Results: Increase in BMAd density was positively correlated with cartilage degradation in MNX mice. OA modified the differentiation capacity of MSCs, accelerating adipocyte differentiation and failing to produce osteoblasts in both human and mice. Human epiphyseal, metaphyseal and SCAT adipocytes from the same OA patients each displayed a specific transcriptome, suggesting different functions. Enrichment analysis defined metaphyseal OA-BMAds as cells implicated in hematopoietic stem cell differentiation. On the other hand, epiphyseal OA-BMAds were considered as osteogenic cells showing an up-regulation of genes related to bone mineralization and remodeling. Specifically, OA epiphysis-secreted molecules decreased ALP activity and altered in vitro the mineralization process.

Conclusion: All these results support the emergence of BMAds as new cell partners in OA, opening new venues for therapeutic approaches.

Figure 1C. Cartilage degradation is positively correlated to bone marrow adiposity in the double MNX mouse model. Perilipin (Plin1) immunofluorescence of SHAM (Scale bar: 800 μm) and MNX (Scale bar: 500 μm) mice at 15 W post-surgery, showing an increased presence of adipocytes in the marrow of the epiphysis and metaphysis of MNX mice. Areas of quantification of Plin1+ cells in the tibiae and femur are highlighted in blue and yellow respectively. Plin1+ cells are shown in red, DAPI in blue. Zoom areas are shown for the tibiae of MNX and SHAM mice showing Plin1+ cells. 

Keywords: Bone marrow adipose tissue; Epiphysis; Mineralization; Osteoarthritis; Subchondral bone.

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